The link between galaxy and black hole growth in the eagle simulation

We investigate the connection between the star formation rate (SFR) of galaxies and their central black hole accretion rate (BHAR) using the EAGLE cosmological hydrodynamical simulation. We find, in striking concurrence with recent observational studies, that the 〈SFR〉–BHAR relation for an active galactic nucleus (AGN)-selected sample produces a relatively flat trend, whilst the 〈BHAR〉–SFR relation for an SFR-selected sample yields an approximately linear trend. These trends remain consistent with their instantaneous equivalents even when both SFR and BHAR are time averaged over a period of 100 Myr. There is no universal relationship between the two growth rates. Instead, SFR and BHAR evolve through distinct paths that depend strongly on the mass of the host dark matter halo. The galaxies hosted by haloes of mass M200 ≲ 1011.5 M⊙ grow steadily, yet black holes (BHs) in these systems hardly grow, yielding a lack of correlation between SFR and BHAR. As haloes grow through the mass range 1011.5 ≲ M200 ≲ 1012.5 M⊙ BHs undergo a rapid phase of non-linear growth. These systems yield a highly non-linear correlation between the SFR and BHAR, which are non-causally connected via the mass of the host halo. In massive haloes (M200 ≳ 1012.5 M⊙), both SFR and BHAR decline on average with a roughly constant scaling of SFR/BHAR ∼ 103. Given the complexity of the full SFR–BHAR plane built from multiple behaviours, and from the large dynamic range of BHARs, we find the primary driver of the different observed trends in the 〈SFR〉–BHAR and 〈BHAR〉–SFR relationships are due to sampling considerably different regions of this plane

Exacerbations of chronic obstructive pulmonary disease: when are antibiotics indicated? A systematic review

BACKGROUND: For decades, there is an unresolved debate about adequate prescription of antibiotics for patients suffering from exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this systematic review was to analyse randomised controlled trials investigating the clinical benefit of antibiotics for COPD exacerbations. METHODS: We conducted a systematic review of randomised, placebo-controlled trials assessing the effects of antibiotics on clinically relevant outcomes in patients with an exacerbation. We searched bibliographic databases, scrutinized reference lists and conference proceedings and asked the pharmaceutical industry for unpublished data. We used fixed-effects models to pool results. The primary outcome was treatment failure of COPD exacerbation treatment. RESULTS: We included 13 trials (1557 patients) of moderate to good quality. For the effects of antibiotics on treatment failure there was much heterogeneity across all trials (I(2 )= 82%). Meta-regression revealed severity of exacerbation as significant explanation for this heterogeneity (p = 0.016): Antibiotics did not reduce treatment failures in outpatients with mild to moderate exacerbations (pooled odds ratio 1.09, 95% CI 0.75–1.59, I(2 )= 18%). Inpatients with severe exacerbations had a substantial benefit on treatment failure rates (pooled odds ratio of 0.25, 95% CI 0.16–0.39, I(2 )= 0%; number-needed to treat of 4, 95% CI 3–5) and on mortality (pooled odds ratio of 0.20, 95% CI 0.06–0.62, I(2 )= 0%; number-needed to treat of 14, 95% CI 12–30). CONCLUSION: Antibiotics effectively reduce treatment failure and mortality rates in COPD patients with severe exacerbations. For patients with mild to moderate exacerbations, antibiotics may not be generally indicated and further research is needed to guide antibiotic prescription in these patients

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Will a rising sea sink some estuarine wetland ecosystems?

Sea-level rise associatedwith climate change presents amajor challenge to plant diversity and ecosystemservice provision in coastal wetlands. In this study,we investigate the effect of sea-level rise on benthos, vegetation, and ecosystem diversity in a tidal wetland in westWales, the UK. Present relationships between plant communities and environmental variableswere investigated through 50 plots atwhich vegetation (species and coverage), hydrological (surface or groundwater depth, conductivity) and soil (matrix chroma, presence or absence ofmottles, organic content, particle size) data were collected. Benthic communities were sampled at intervals along a continuum from saline to freshwater. To ascertain future changes to the wetlands' hydrology, a GIS-based empirical model was developed. Using a LiDAR derived land surface, the relative effect of peat accumulation and rising sea levels were modelled over 200 years to determine how frequently portions of the wetland will be inundated by mean sea level, mean high water spring and mean high water neap conditions. The model takes into account changing extents of peat accumulation as hydrological conditions alter. Model results show that changes to the wetland hydrology will initially be slow. However, changes in frequency and extent of inundation reach a tipping point 125 to 175 years from2010 due to the extremely low slope of the wetland. From then onwards, large portions of the wetland become flooded at every flood tide and saltwater intrusion becomes more common. This will result in a reduction in marsh biodiversity with plant communities switching toward less diverse and occasionally monospecific communities that are more salt tolerant.IS

Star clusters near and far; tracing star formation across cosmic time

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00690-x.Star clusters are fundamental units of stellar feedback and unique tracers of their host galactic properties. In this review, we will first focus on their constituents, i.e.\ detailed insight into their stellar populations and their surrounding ionised, warm, neutral, and molecular gas. We, then, move beyond the Local Group to review star cluster populations at various evolutionary stages, and in diverse galactic environmental conditions accessible in the local Universe. At high redshift, where conditions for cluster formation and evolution are more extreme, we are only able to observe the integrated light of a handful of objects that we believe will become globular clusters. We therefore discuss how numerical and analytical methods, informed by the observed properties of cluster populations in the local Universe, are used to develop sophisticated simulations potentially capable of disentangling the genetic map of galaxy formation and assembly that is carried by globular cluster populations.Peer reviewedFinal Accepted Versio

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

A MODEST review

We present an account of the state of the art in the fields explored by the research community invested in 'Modeling and Observing DEnse STellar systems'. For this purpose, we take as a basis the activities of the MODEST-17 conference, which was held at Charles University, Prague, in September 2017. Reviewed topics include recent advances in fundamental stellar dynamics, numerical methods for the solution of the gravitational N-body problem, formation and evolution of young and old star clusters and galactic nuclei, their elusive stellar populations, planetary systems, and exotic compact objects, with timely attention to black holes of different classes of mass and their role as sources of gravitational waves. Such a breadth of topics reflects the growing role played by collisional stellar dynamics in numerous areas of modern astrophysics. Indeed, in the next decade, many revolutionary instruments will enable the derivation of positions and velocities of individual stars in the Milky Way and its satellites and will detect signals from a range of astrophysical sources in different portions of the electromagnetic and gravitational spectrum, with an unprecedented sensitivity. On the one hand, this wealth of data will allow us to address a number of long-standing open questions in star cluster studies; on the other hand, many unexpected properties of these systems will come to light, stimulating further progress of our understanding of their formation and evolution.Comment: 42 pages; accepted for publication in 'Computational Astrophysics and Cosmology'. We are much grateful to the organisers of the MODEST-17 conference (Charles University, Prague, September 2017). We acknowledge the input provided by all MODEST-17 participants, and, more generally, by the members of the MODEST communit

Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics

The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Renal cell carcinoma(RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival

Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis